Panels of monoclonal antibodies and cDNA probes to lineage restricted and other genes are being used to thoroughly characterize B lymphocyte progenitors in the mouse. The objective is to establish a temporal sequence in which genes are expressed and/or repressed during differentiation and relate these to the rearrangement and usage of immunoglobulin genes. Soluble mediators, including a new pre-B cell growth factor, are being used to influence these events in short term cultures and long term cultures are being used to study microenvironmental elements which may normally elaborate such stimuli. Antibodies and gene probes are being used to characterize clones of stromal cells isolated from this model with a view to learning their diversity and developmental origins. Attempts will be made to understand how physical relationships between cells and directed migration are achieved within bone marrow and this will be related to immunohistochemical studies of marrow architecture. The basic information about the cellular and molecular requirements for B lymphocyte formation should contribute to our overall understanding of this differentiation sequence and may have practical implications relative to human disease.